Despite significant progress in defining the molecular mechanisms governing allograft rejection, historical improvements in clinical transplant outcomes have plateaued and are currently achieved at the cost of chronic broad-spectrum immunosuppression. Induction of donor- specific tolerance offers the best hope of achieving better results. A focused approach targeting the specific cellular events governing the rejection response appears to be the most promising strategy to achieve this objective, and, if effective, clearly would be preferable to the broad-spectrum immunosuppression currently available. The interaction between CD40, a cell surface molecule expressed on B- cells and antigen-presenting cells, and its T-cell ligand, CD40-L, appears to be pivotal to induction of the immune responses which require T-cell help, including allograft rejection and responses to some infectious agents. The cellular and molecular mechanisms governing the effects of anti CD40-L antibody on intragraft cytokine production, antidonor antibody production, and antibody responses to T-cell dependent viral antigens will be investigated in a heterotopic cynomolgus monkey transplant model. This study is likely to contribute to the understanding of the mechanisms by which the CD40L-dependent cellular interactions influence allograft rejection and viral immunity in a clinically relevant model, and thus to progress toward safer and more successful transplantation.